Clinical Trial Results:
A Phase III, Double-Blind, Randomized, Placebo-Controlled Cross-Over Clinical Trial to Study the Efficacy and Safety of MK-0476 in Japanese Pediatric Subjects with Seasonal Allergic Rhinitis
Summary
|
|
EudraCT number |
2014-004774-42 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
01 Sep 2013
|
Results information
|
|
Results version number |
v1 |
This version publication date |
01 Mar 2016
|
First version publication date |
09 Jul 2015
|
Other versions |
v2 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
0476-519
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01857063 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
MK-0476-519: Merck protocol number | ||
Sponsors
|
|||
Sponsor organisation name |
Merck Sharp & Dohme Corp.
|
||
Sponsor organisation address |
2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
|
||
Public contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
|
||
Scientific contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
01 Sep 2013
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
01 Sep 2013
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
01 Sep 2013
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
This study will evaluate the efficacy and safety of montelukast (MK-0476) in the treatment of Japanese pediatric participants with seasonal allergic rhinitis (SAR). The primary hypothesis of this study is that montelukast is superior to placebo in the treatment of nasal symptoms in SAR.
|
||
Protection of trial subjects |
This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
10 Jun 2013
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Japan: 220
|
||
Worldwide total number of subjects |
220
|
||
EEA total number of subjects |
0
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
68
|
||
Adolescents (12-17 years) |
152
|
||
Adults (18-64 years) |
0
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
|
||||||||||||||||||||||
Recruitment
|
||||||||||||||||||||||
Recruitment details |
- | |||||||||||||||||||||
Pre-assignment
|
||||||||||||||||||||||
Screening details |
Japanese participants aged 10 to 15 years who had allergic rhinitis symptoms (Japanese Cedar [JC] pollinosis) were screened for this study. | |||||||||||||||||||||
Period 1
|
||||||||||||||||||||||
Period 1 title |
Treatment Period 1 (7 days)
|
|||||||||||||||||||||
Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
|
|||||||||||||||||||||
Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | |||||||||||||||||||||
Arms
|
||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||
Arm title
|
Montelukast/Placebo | |||||||||||||||||||||
Arm description |
Participants receive montelukast 5 mg chewable tablets for 7 days during Treatment Period 1 and receive placebo chewable tablets for 7 days during Treatment Period 2. There is a 7-day washout period between Treatment Periods 1 and 2. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Montelukast
|
|||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||
Other name |
MK-0476
|
|||||||||||||||||||||
Pharmaceutical forms |
Chewable tablet
|
|||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||
Dosage and administration details |
Montelukast 5 mg chewable tablets orally once daily for 7 days
|
|||||||||||||||||||||
Investigational medicinal product name |
Placebo
|
|||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||
Other name |
||||||||||||||||||||||
Pharmaceutical forms |
Chewable tablet
|
|||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||
Dosage and administration details |
Placebo chewable tablets orally once daily for 7 days
|
|||||||||||||||||||||
Arm title
|
Placebo/Montelukast | |||||||||||||||||||||
Arm description |
Participants receive placebo chewable tablets for 7 days during Treatment Period 1 and receive montelukast 5 mg chewable tablets for 7 days during Treatment Period 2. There is a 7-day washout period between Treatment Periods 1 and 2. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Placebo
|
|||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||
Other name |
||||||||||||||||||||||
Pharmaceutical forms |
Chewable tablet
|
|||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||
Dosage and administration details |
Placebo chewable tablets orally once daily for 7 days
|
|||||||||||||||||||||
Investigational medicinal product name |
Montelukast
|
|||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||
Other name |
MK-0476
|
|||||||||||||||||||||
Pharmaceutical forms |
Chewable tablet
|
|||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||
Dosage and administration details |
Montelukast 5 mg chewable tablets orally once daily for 7 days
|
|||||||||||||||||||||
|
||||||||||||||||||||||
Period 2
|
||||||||||||||||||||||
Period 2 title |
Treatment Period 2 (7 days)
|
|||||||||||||||||||||
Is this the baseline period? |
No | |||||||||||||||||||||
Allocation method |
Randomised - controlled
|
|||||||||||||||||||||
Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | |||||||||||||||||||||
Arms
|
||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||
Arm title
|
Placebo/Montelukast | |||||||||||||||||||||
Arm description |
Participants receive placebo chewable tablets for 7 days during Treatment Period 1 and receive montelukast 5 mg chewable tablets for 7 days during Treatment Period 2. There is a 7-day washout period between Treatment Periods 1 and 2. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Placebo
|
|||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||
Other name |
||||||||||||||||||||||
Pharmaceutical forms |
Chewable tablet
|
|||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||
Dosage and administration details |
Placebo chewable tablets orally once daily for 7 days
|
|||||||||||||||||||||
Investigational medicinal product name |
Montelukast
|
|||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||
Other name |
MK-0476
|
|||||||||||||||||||||
Pharmaceutical forms |
Chewable tablet
|
|||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||
Dosage and administration details |
Montelukast 5 mg chewable tablets orally once daily for 7 days
|
|||||||||||||||||||||
Arm title
|
Montelukast/Placebo | |||||||||||||||||||||
Arm description |
Participants receive montelukast 5 mg chewable tablets for 7 days during Treatment Period 1 and receive placebo chewable tablets for 7 days during Treatment Period 2. There is a 7-day washout period between Treatment Periods 1 and 2. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Montelukast
|
|||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||
Other name |
MK-0476
|
|||||||||||||||||||||
Pharmaceutical forms |
Chewable tablet
|
|||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||
Dosage and administration details |
Montelukast 5 mg chewable tablets orally once daily for 7 days
|
|||||||||||||||||||||
Investigational medicinal product name |
Placebo
|
|||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||
Other name |
||||||||||||||||||||||
Pharmaceutical forms |
Chewable tablet
|
|||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||
Dosage and administration details |
Placebo chewable tablets orally once daily for 7 days
|
|||||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Montelukast/Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants receive montelukast 5 mg chewable tablets for 7 days during Treatment Period 1 and receive placebo chewable tablets for 7 days during Treatment Period 2. There is a 7-day washout period between Treatment Periods 1 and 2. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo/Montelukast
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants receive placebo chewable tablets for 7 days during Treatment Period 1 and receive montelukast 5 mg chewable tablets for 7 days during Treatment Period 2. There is a 7-day washout period between Treatment Periods 1 and 2. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Montelukast/Placebo
|
||
Reporting group description |
Participants receive montelukast 5 mg chewable tablets for 7 days during Treatment Period 1 and receive placebo chewable tablets for 7 days during Treatment Period 2. There is a 7-day washout period between Treatment Periods 1 and 2. | ||
Reporting group title |
Placebo/Montelukast
|
||
Reporting group description |
Participants receive placebo chewable tablets for 7 days during Treatment Period 1 and receive montelukast 5 mg chewable tablets for 7 days during Treatment Period 2. There is a 7-day washout period between Treatment Periods 1 and 2. | ||
Reporting group title |
Placebo/Montelukast
|
||
Reporting group description |
Participants receive placebo chewable tablets for 7 days during Treatment Period 1 and receive montelukast 5 mg chewable tablets for 7 days during Treatment Period 2. There is a 7-day washout period between Treatment Periods 1 and 2. | ||
Reporting group title |
Montelukast/Placebo
|
||
Reporting group description |
Participants receive montelukast 5 mg chewable tablets for 7 days during Treatment Period 1 and receive placebo chewable tablets for 7 days during Treatment Period 2. There is a 7-day washout period between Treatment Periods 1 and 2. | ||
Subject analysis set title |
Montelukast - Efficacy
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Participants receive montelukast 5 mg for 7 days, regardless of sequence. Efficacy analysis set includes all randomized participants who took at least one dose of study drug (montelukast), and had a baseline assessment and at least one post-baseline assessment in a treatment period.
|
||
Subject analysis set title |
Montelukast - Safety
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants receive montelukast 5 mg for 7 days, regardless of sequence. Safety analysis set includes all randomized participants who received at least one dose of study drug (montelukast). Adverse events (AEs) are reported by study drug (montelukast) taken at time of the event.
|
||
Subject analysis set title |
Placebo - Safety
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants receive placebo for 7 days, regardless of sequence. Safety analysis set includes all randomized participants who received at least one dose of study drug (placebo for montelukast). Adverse events (AEs) are reported by study drug (placebo for montelukast) taken at time of the event.
|
||
Subject analysis set title |
Placebo - Efficacy
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Participants receive placebo for 7 days, regardless of sequence. Efficacy analysis set includes all randomized participants who took at least one dose of study drug (placebo for montelukast), and had a baseline assessment and at least one post-baseline assessment in a treatment period.
|
|
|||||||||||||
End point title |
Change from Baseline in Total Nasal Symptom Score (TNSS) Averaged During 3 Hours of Exposure | ||||||||||||
End point description |
The TNSS is the sum of the three nasal symptom scores for nasal congestion, nasal discharge and sneezing. Participants completed a questionnaire about their nasal symptoms. Scores ranged from 0 to 4 for each of the three nasal symptoms, with a total possible score ranging from 0 to 12 and a higher score indicating more severe nasal symptoms. The Baseline TNSS was assessed on Day 7 of a treatment period prior to entering the chamber room. The post-Baseline TNSS was assessed on Day 7 of a treatment period during 3 hours of exposure to JC pollen in the chamber room, as an average of measurements at 30, 60, 90, 120, 150 and 180 minutes. Analysis was done by study drug as taken.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Baseline and after 3 hours of pollen exposure on Day 7 of each treatment period
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in least squares (LS) means | ||||||||||||
Statistical analysis description |
Difference in LS means of change from Baseline in TNSS averaged during 3 hours of exposure - Montelukast vs. Placebo. Based on longitudinal data analysis (LDA) model with Baseline TNSS as a covariate, sequence, treatment and period as fixed effects and participants as a random effect.
|
||||||||||||
Comparison groups |
Montelukast - Efficacy v Placebo - Efficacy
|
||||||||||||
Number of subjects included in analysis |
424
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.913 [1] | ||||||||||||
Method |
Longitudinal Data Analysis (LDA) | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.01
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.11 | ||||||||||||
upper limit |
0.1 | ||||||||||||
Notes [1] - LDA model with baseline TNSS as a covariate, sequence, treatment and period as fixed effects and participant as a random effect. |
|
|||||||||||||
End point title |
Percentage of Participants Who Experience at Least One Adverse Event [2] | ||||||||||||
End point description |
An adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Participants were monitored for occurrence adverse events for up to 14 days after last dose of study drug. Analysis was done by study drug as taken.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Up to 5 weeks
|
||||||||||||
Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this end point. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from Baseline in Weighted TNSS Averaged During 3 Hours of Exposure | ||||||||||||
End point description |
TNSS was weighted as 2:1:1 for nasal congestion, nasal discharge and sneezing. The Weighted TNSS ranged from 0 to 16, with a higher score indicating more severe weighted total nasal symptoms. The Baseline Weighted TNSS was assessed on Day 7 of a treatment period prior to entering the chamber room. The post-Baseline TNSS was assessed on Day 7 of a treatment period during 3 hours of exposure to JC pollen in the chamber room, as an average of measurements at 30, 60, 90, 120, 150 and 180 minutes. Analysis was done by study drug as taken.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and after 3 hours of pollen exposure on Day 7 of each treatment period
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in LS means | ||||||||||||
Statistical analysis description |
Difference in LS means for change from Baseline in weighted TNSS averaged during 3 hours of exposure - Montelukast vs. Placebo. Based on LDA model with Baseline weighted TNSS as a covariate, sequence, treatment and period as fixed effects and participants as a random effect.
|
||||||||||||
Comparison groups |
Montelukast - Efficacy v Placebo - Efficacy
|
||||||||||||
Number of subjects included in analysis |
424
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.953 [3] | ||||||||||||
Method |
LDA | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.17 | ||||||||||||
upper limit |
0.16 | ||||||||||||
Notes [3] - LDA model with baseline Weighted TNSS as a covariate, sequence, treatment and period as fixed effects and participant as a random effect. |
|
|||||||||||||
End point title |
Change from Baseline in Nasal Congestion Score Averaged During 3 Hours of Exposure | ||||||||||||
End point description |
The Nasal Congestion Score was assessed as 0 = No symptoms of nasal congestion to 4 = Completely obstructed all day, with a possible Nasal Congestion Score ranging from 0 to 4 and a higher score indicating more severe nasal congestion. The Baseline Nasal Congestion Score was assessed on Day 7 of a treatment period prior to entering the chamber room. The post-Baseline Nasal Congestion Score was assessed on Day 7 of a treatment period during 3 hours of exposure to JC pollen in the chamber room, as an average of measurements at 30, 60, 90, 120, 150 and 180 minutes. Analysis was done by study drug as taken.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and after 3 hours of pollen exposure on Day 7 of each treatment period
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in LS means | ||||||||||||
Statistical analysis description |
Difference in LS means of change from Baseline in Nasal Congestion Score averaged during 3 hours of exposures - Montelukast vs. Placebo. Based on LDA model with Baseline Nasal Congestion Score as a coavariate, sequence, treatment and period as fixed effects and participants as a random effect.
|
||||||||||||
Comparison groups |
Montelukast - Efficacy v Placebo - Efficacy
|
||||||||||||
Number of subjects included in analysis |
424
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.974 [4] | ||||||||||||
Method |
LDA | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.07 | ||||||||||||
upper limit |
0.07 | ||||||||||||
Notes [4] - LDA model with baseline nasal congestion score as a covariate, sequence, treatment and period as fixed effects and participant as a random effect. |
|
|||||||||||||
End point title |
Change from Baseline in Nasal Discharge Score Averaged During 3 Hours of Exposure | ||||||||||||
End point description |
The Nasal Discharge Score was assessed as 0 = 0 times participant blew his/her nose to 4 = 21 or more times participant blew his/her nose, with a possible Nasal Discharge Score ranging from 0 to 4 and a higher score indicating more severe nasal discharge. The Baseline Nasal Discharge Score was assessed on Day 7 of a treatment period prior to entering the chamber room. The post-Baseline Nasal Discharge Score was assessed on Day 7 of a treatment period during 3 hours of exposure to JC pollen in the chamber room, as an average of measurements at 30, 60, 90, 120, 150 and 180 minutes. Analysis was done by study drug as taken.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and after 3 hours of pollen exposure on Day 7 of each treatment period
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in LS means | ||||||||||||
Statistical analysis description |
Difference in LS means for change from Baseline in Nasal Discharge Score averaged during 3 hours of exposure - Montelukast vs. Placebo. Based on LDA model with Baseline Nasal Discharge Score as a covariate, sequence, treatment and period as fixed effects and participant as a random effect.
|
||||||||||||
Comparison groups |
Montelukast - Efficacy v Placebo - Efficacy
|
||||||||||||
Number of subjects included in analysis |
424
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.182 [5] | ||||||||||||
Method |
LDA | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.03
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.06 | ||||||||||||
upper limit |
0.01 | ||||||||||||
Notes [5] - LDA model with baseline nasal discharge score as a covariate, sequence, treatment and period as fixed effects and participant as a random effect. |
|
|||||||||||||
End point title |
Change from Baseline in Sneezing Score Averaged During 3 Hours of Exposure | ||||||||||||
End point description |
The Sneezing Score was assessed as 0 = 0 times participant sneezed to 4 = 21 or more times participant sneezed, with a possible Sneezing Score ranging from 0 to 4 and a higher score indicating more severe sneezing. The Baseline Sneezing Score was assessed on Day 7 of a treatment period prior to entering the chamber room. The post-Baseline Sneezing Score was assessed on Day 7 of a treatment period during 3 hours of exposure to JC pollen in the chamber room, as an average of measurements at 30, 60, 90, 120, 150 and 180 minutes. Analysis was done by study drug as taken.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and after 3 hours of pollen exposure on Day 7 of each treatment period
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in LS means | ||||||||||||
Statistical analysis description |
Difference in LS means for change from Baseline in Sneezing Score averaged during 3 hours of exposure - Montelukast vs. Placebo. Based on LDA model with Baseline Sneezing Score as a covariate, sequence, treatment and period as fixed effects and participant as a random effect.
|
||||||||||||
Comparison groups |
Montelukast - Efficacy v Placebo - Efficacy
|
||||||||||||
Number of subjects included in analysis |
424
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.161 [6] | ||||||||||||
Method |
LDA | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.02
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.01 | ||||||||||||
upper limit |
0.05 | ||||||||||||
Notes [6] - LDA model with baseline sneezing score as a covariate, sequence, treatment and period as fixed effects and participant as a random effect. |
|
|||||||||||||||||||||||||||||||
End point title |
Change from Baseline in TNSS at 30, 60, 90, 120, 150 and 180 Minutes After Entering Chamber Room | ||||||||||||||||||||||||||||||
End point description |
The TNSS is the sum of the three nasal symptom scores for nasal congestion, nasal discharge and sneezing. The possible TNSS ranged from 0 to 12, with a higher score indicting more severe total nasal symptoms. The Baseline TNSS was assessed on Day 7 of a treatment period prior to entering the chamber room. The post-Baseline TNSS was assessed on Day 7 of a treatment period at 30, 60, 90, 120, 150 and 180 minutes after entering the chamber room. Analysis was done by study drug as taken.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Baseline and at 30, 60, 90, 120, 150 and 180 minutes after entering chamber room on Day 7 of a treatment period
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||
End point title |
Change from Baseline in Weighted TNSS at 30, 60, 90, 120, 150 and 180 Minutes After Entering Chamber Room | ||||||||||||||||||||||||||||||
End point description |
TNSS was weighted as 2:1:1 for nasal congestion, nasal discharge and sneezing. The possible Weighted TNSS ranged from 0 to 16, with a higher score indicating more severe total nasal symptoms. The Baseline TNSS was assessed on Day 7 of a treatment period prior to entering the chamber room. The post-Baseline Weighted TNSS was assessed on Day 7 of a treatment period at 30, 60, 90, 120, 150 and 180 minutes after entering the chamber room. Analysis was done by study drug as taken.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Baseline and at 30, 60, 90, 120, 150 and 180 minutes after entering chamber room on Day 7 of a treatment period
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||
End point title |
Change from Baseline in Nasal Congestion Score at 30, 60, 90, 120, 150 and 180 Minutes After Entering Chamber Room | ||||||||||||||||||||||||||||||
End point description |
The Nasal Congestion Score was assessed as 0 = No symptoms of nasal congestion to 4 = Completely obstructed all day. The possible Nasal Congestion Score ranged from 0 to 4, with a higher score indicating more severe nasal congestion.The Nasal Congestion Score was assessed on Day 7 prior to entering the chamber room and at 30, 60, 90, 120, 150 and 180 minutes after entering the chamber room. Analysis was done by study drug as taken.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Baseline and at 30, 60, 90, 120, 150 and 180 minutes after entering chamber room on Day 7 of a treatment period
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||
End point title |
Change from Baseline in Nasal Discharge Score at 30, 60, 90, 120, 150 and 180 Minutes After Entering Chamber Room | ||||||||||||||||||||||||||||||
End point description |
The Nasal Discharge Score was assessed as 0 = 0 times participant blew his/her nose to 4 = 21 or more times participant blew his/her nose. The possible Nasal Discharge Score ranged from 0 to 4, with a higher score indicating more severe nasal discharge. The Nasal Discharge Score was assessed on Day 7 prior to entering the chamber room and at 30, 60, 90, 120, 150 and 180 minutes after entering the chamber room. Analysis was done by study drug as taken.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Baseline and at 30, 60, 90, 120, 150 and 180 minutes after entering chamber room on Day 7 of a treatment period
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||
End point title |
Change from Baseline in Sneezing Score at 30, 60, 90, 120, 150 and 180 Minutes After Entering Chamber Room | ||||||||||||||||||||||||||||||
End point description |
The Sneezing Score was assessed as 0 = 0 times participant sneezed to 4 = 21 or more times participant sneezed. The possible Sneezing Score ranged from 0 to 4, with a higher score indicating more severe sneezing. The Sneezing Score was assessed on Day 7 prior to entering the chamber room and at 30, 60, 90, 120, 150 and 180 minutes after entering the chamber room. Analysis was done by study drug as taken.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Baseline and at 30, 60, 90, 120, 150 and 180 minutes after entering chamber room on Day 7 of a treatment period
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
Adverse events information
|
||||||||||||||||||||||
Timeframe for reporting adverse events |
Up to 14 days after last dose of study drug (Up to 5 weeks)
|
|||||||||||||||||||||
Adverse event reporting additional description |
The All Participants as Treated (APaT) population consisted of all randomized participants who received at least one dose of study drug. AEs are reported by dose taken at time of the AE and not by randomly assigned sequence.
|
|||||||||||||||||||||
Assessment type |
Systematic | |||||||||||||||||||||
Dictionary used for adverse event reporting
|
||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||
Dictionary version |
16.0
|
|||||||||||||||||||||
Reporting groups
|
||||||||||||||||||||||
Reporting group title |
Placebo
|
|||||||||||||||||||||
Reporting group description |
Participants receive placebo for 7 days, regardless of sequence. | |||||||||||||||||||||
Reporting group title |
Montelukast
|
|||||||||||||||||||||
Reporting group description |
Participants receive montelukast 5 mg for 7 days, regardless of sequence. | |||||||||||||||||||||
|
||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |